Propofol treatment correlates with changes in pain sensitivity and thalamocortical glutamate/GABA balance in sleep-deprived mice

Sleep disorders profoundly impair patients' daily quality of life and present substantial challenges to clinical management. Accumulating evidence has shown that propofol improves sleep architecture and quality in clinical practice, yet its mechanism in modulating pain linked to sleep disorders remains elusive. Given that chronic sleep disruption is often accompanied by impaired pain thresholds and imbalances between excitatory and inhibitory neurotransmitters, this study aimed to determine whether propofol alleviates sleep-deprivation-induced pain threshold reduction by modulating this neurotransmitter balance.

A modified multi-platform water maze was used to establish a sleep-deprived mouse model simulating sleep disruption. Following tail vein administration of varying propofol doses, behavioral assessments were conducted to evaluate its effects on sleep states and pain thresholds. Concurrently, electroencephalogram (EEG) and electromyogram (EMG) recordings captured sleep rhythm alterations. To further investigate neurochemical mechanisms, 9.4 T MRI and amino acid metabolism analysis were employed to obtain magnetic resonance spectroscopy (MRS) data. Glutamate (Glu) and γ-aminobutyric acid (GABA) levels in the thalamus and cortex were measured to assess dynamic changes in the excitatory/inhibitory neurotransmitter balance.

Our results demonstrated that sleep deprivation significantly reduced the pain threshold in mice, which was accompanied by an imbalance in the thalamocortical Glu/GABA ratio. Propofol intervention markedly restored this neurotransmitter imbalance - the Glu/GABA metabolic ratio returned to a relatively stable level, and the reduced pain threshold was significantly improved. Concurrent EEG and EMG recordings revealed that propofol optimized sleep architecture and partially reversed sleep rhythm disturbances caused by sleep deprivation.

In summary, propofol effectively alleviates sleep-deprivation-induced pain reduction in pain threshold. This analgesic effect is associated with the restoration of the dynamic equilibrium of excitatory/inhibitory neurotransmitters (Glu/GABA) in the thalamocortical circuit. Our findings provide novel experimental and neurochemical evidence supporting the potential application of propofol in sleep disorders and associated pain management, thereby offering a valuable reference for future clinical translational research.